The purpose of this project is to evaluate the immune response to viruses in healthy individuals and to identify abnormalities in these responses which may be related to the disease mechanisms. These studies focus on functional analysis of the cellular immune response to viruses which commonly affect humans and which may be involved in diseases of the nervous system. The mechanisms involved in the regulation of these responses are being examined. An additional goal of these studies is to evaluate the influence of genetic makeup on both induction and effector phases of the immune response to viruses. Assays for cytotoxic T cells, and helper T cells specific are employed. Virus antigens recognized by these cell populations and the influence of antigen presentation on the generation of these responses are being examined. These studies use techniques of molecular biology to incorporate the genes of particular virus proteins into appropriate target cells. Finally, in these investigations, findings obtained in healthy individuals are applied to the evaluation of patients with the diseases of the nervous system, particularly multiple sclerosis (MS) which may involve immunological or infectious mechanisms. Emphasis is on identification of the mechanisms of reduced generation of measles virus-specific CTL in patients with MS. Longitudinal studies of both normal individuals and patients are conducted.